Alzheimer's disease and Parkinson's disease are characterized by the presence of abnormal filamentous assemblies within some nerve cells. Similar assemblies are found in related disorders, including progressive supranuclear palsy, dementia with Lewy bodies, multiple system atrophy, corticobasal degeneration and Pick's disease. The events leading to filament formation or the mere presence of filaments are believed to produce nerve cell degeneration. Our work has shown that the intraneuronal filaments found in these diseases are made of either microtubule-associated protein tau or alpha-synuclein. Mutations in the tau gene cause inherited forms of frontotemporal dementia and parkinsonism, whereas mutations in the alpha-synuclein gene cause familial forms of Parkinson's disease and dementia with Lewy bodies. Current work is aimed at developing experimental animal models of tauopathies and alpha-synucleinopathies and at identifying disease modifiers.